Ischemia
or ischaemia is a restriction in
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
supply to any
tissue,
muscle group, or
organ
Organ may refer to:
Biology
* Organ (biology), a part of an organism
Musical instruments
* Organ (music), a family of keyboard musical instruments characterized by sustained tone
** Electronic organ, an electronic keyboard instrument
** Hammond ...
of the body, causing a shortage of
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...
that is needed for
cellular metabolism (to keep tissue alive).
Ischemia is generally caused by problems with
blood vessel
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide awa ...
s, with resultant damage to or dysfunction of tissue i.e.
hypoxia and
microvascular dysfunction. It also implies local
hypoxia in a part of a body resulting from
constriction
Constriction is a method used by various snake species to kill or subdue their prey. Although some species of venomous and mildly venomous snakes do use constriction to subdue their prey, most snakes which use constriction lack venom. The snake i ...
(such as
vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
,
thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
, or
embolism). Ischemia causes not only insufficiency of oxygen, but also reduced availability of
nutrients and inadequate removal of
metabolic wastes. Ischemia can be partial (poor
perfusion) or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce
chronotrophy and
ionotrophy to meet the new level of blood delivery supplied by the
stenosed vasculature so that it is adequate.
Signs and symptoms
The signs and symptoms of ischemia vary, as they can occur anywhere in the body and depend on the degree to which blood flow is interrupted.
For example, clinical manifestations of
acute limb ischemia
Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb.
Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma. Thrombosis is usually caused by peripheral vascular disease (athe ...
(which can be summarized as the "six P's") include
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
,
pallor,
pulseless,
paresthesia,
paralysis, and
poikilothermia.
Without immediate intervention, ischemia may progress quickly to tissue
necrosis and
gangrene within a few hours.
Paralysis is a very late sign of acute arterial ischemia and signals the death of
nerves supplying the extremity.
Foot drop
Foot drop is a gait abnormality in which the dropping of the forefoot happens due to weakness, irritation or damage to the deep fibular nerve (deep peroneal), including the sciatic nerve, or paralysis of the muscles in the anterior portion of t ...
may occur as a result of
nerve damage. Because nerves are extremely sensitive to
hypoxia, limb
paralysis or ischemic
neuropathy may persist after
revascularization and may be permanent.
[
]
Cardiac ischemia
Cardiac ischemia may be asymptomatic or may cause chest pain, known as angina pectoris. It occurs when the heart muscle, or myocardium
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...
, receives insufficient blood flow. This most frequently results from atherosclerosis, which is the long-term accumulation of cholesterol-rich plaques in the coronary arteries
The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ ...
. In most Western countries, Ischemic heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...
is the most common cause of death in both men and women, and a major cause of hospital admissions.
Bowel
Both large and small intestines can be affected by ischemia. The blockage of blood flow to the large intestine (colon) is called ischemic colitis
Ischemic colitis (also spelled ischaemic colitis) is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater ...
. Ischemia of the small bowel is called mesenteric ischemia.
Brain
Brain ischemia is insufficient blood flow to the brain
A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...
, and can be acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse ef ...
or chronic. Acute ischemic stroke is a neurological emergency typically caused by a blood clot blocking blood flow in a vessel in the brain. Chronic ischemia of the brain may result in a form of dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
called vascular dementia
Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting ...
. A sudden, brief episode (symptoms lasting only minutes) of ischemia affecting the brain is called a transient ischemic attack (TIA), often called a mini-stroke. TIAs can be a warning of future strokes, with approximately 1/3 of TIA patients having a serious stroke within one year.
Limb
Inadequate blood supply to a limb
Limb may refer to:
Science and technology
* Limb (anatomy), an appendage of a human or animal
*Limb, a large or main branch of a tree
*Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb
*Limb, in botany, ...
may results in acute limb ischemia
Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb.
Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma. Thrombosis is usually caused by peripheral vascular disease (athe ...
or chronic limb threatening ischemia.
Cutaneous
Reduced blood flow to the skin layers may result in mottling or uneven, patchy discoloration of the skin.
Kidney Ischemia
Kidney Ischemia is a loss of blood flow to the kidney cells. Several physical symptoms include shrinkage of one or both kidneys, renovascular hypertension
Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to l ...
, acute renal failure, progressive azotemia, and acute pulmonary edema
Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due ...
. It is a disease with high mortality rate and high morbidity. Failure to treat could cause chronic kidney disease and a need for renal surgery.
Causes
Ischemia is a vascular disease
Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause a ...
involving an interruption in the arterial blood supply
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
to a tissue, organ
Organ may refer to:
Biology
* Organ (biology), a part of an organism
Musical instruments
* Organ (music), a family of keyboard musical instruments characterized by sustained tone
** Electronic organ, an electronic keyboard instrument
** Hammond ...
, or extremity that, if untreated, can lead to tissue death. It can be caused by embolism, thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
of an atherosclerotic artery, or trauma. Venous problems like venous outflow obstruction and low-flow states can cause acute arterial ischemia. An aneurysm
An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ( ...
is one of the most frequent causes of acute arterial ischemia. Other causes are heart conditions including myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
, mitral valve disease
Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. , chronic atrial fibrillation, cardiomyopathies, and prosthesis, in all of which thrombi are prone to develop.[Lewis. S.L (2008). ''Medical-Surgical Nursing'' (7th ed.). Vascular disorder. pp. 907–908.]
Occlusion
The thrombi may dislodge and may travel anywhere in the circulatory system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
, where they may lead to pulmonary embolus, an acute arterial occlusion causing the oxygen and blood supply
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
distal to the embolus to decrease suddenly. The degree and extent of symptoms depend on the size and location of the obstruction, the occurrence of clot fragmentation with embolism to smaller vessels, and the degree of peripheral arterial disease
Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular dise ...
(PAD).[
* ]Thromboembolism
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets ...
(blood clots)
* Embolism (foreign bodies in the circulation, e.g. amniotic fluid embolism
An amniotic fluid embolism (AFE) is a very uncommon childbirth ( obstetric) emergency in which amniotic fluid enters the blood stream of the mother, triggering a serious reaction, which results in cardiorespiratory (heart and lung) collapse and ...
)
Trauma
Traumatic injury to an extremity may produce partial or total occlusion of a vessel from compression, shearing
Sheep shearing is the process by which the woollen fleece of a sheep is cut off. The person who removes the sheep's wool is called a '' shearer''. Typically each adult sheep is shorn once each year (a sheep may be said to have been "shorn" o ...
, or laceration
A wound is a rapid onset of injury that involves lacerated or punctured skin (an ''open'' wound), or a contusion (a ''closed'' wound) from blunt force trauma or compression. In pathology, a ''wound'' is an acute injury that damages the epid ...
. Acute arterial occlusion may develop as a result of arterial dissection in the carotid artery or aorta or as a result of iatrogenic arterial injury (e.g., after angiography).[
]
Other
An inadequate flow of blood to a part of the body may be caused by any of the following:
* Thoracic outlet syndrome (compression of the brachial plexus)
* Atherosclerosis (lipid-laden plaques obstructing the lumen of arteries)
* Hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
(lower than normal level of glucose)
* Tachycardia (abnormally rapid beating of the heart
The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...
)
* Radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
* Hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...
(low blood pressure, e.g. in septic shock, heart failure)
* Outside compression of a blood vessel, e.g. by a tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
or in the case of superior mesenteric artery syndrome
* Sickle cell disease (abnormally shaped red blood cells)
* Induced g-force
The gravitational force equivalent, or, more commonly, g-force, is a measurement of the type of force per unit mass – typically acceleration – that causes a perception of weight, with a g-force of 1 g (not gram in mass measur ...
s which restrict the blood flow and force the blood to the extremities of the body, as in acrobatics and military flying
* Localized extreme cold, such as by frostbite
Frostbite is a skin injury that occurs when exposed to extreme low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occurs in t ...
or improper cold compression therapy
Cold compression therapy, also known as hilotherapy, combines two of the principles of rest, ice, compression, elevation to reduce pain and swelling from a sports or activity injury to soft tissues and is recommended by orthopedic surgeons follow ...
* Tourniquet
A tourniquet is a device that is used to apply pressure to a limb or extremity in order to stop the flow of blood. It may be used in emergencies, in surgery, or in post-operative rehabilitation.
A simple tourniquet can be made from a stick an ...
application
* An increased level of glutamate receptor
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...
stimulation
* Arteriovenous malformations and peripheral artery occlusive disease
* rupture of significant blood vessels supplying a tissue or organ.
* Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
vasoconstricts the periphery so that red blood cells cannot work internally on vital organs such as the heart, brain, etc., thus causing lack of oxygen to the periphery.
* Premature discontinuation of any oral anticoagulant.
* Unconsciousness
Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the r ...
, such as due to the ingestion of excessive doses of central depressants like alcohol or opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
s, can result in ischemia of the extremities due to unusual body positions that prevent normal circulation
Pathophysiology
Ischemia results in tissue damage in a process known as ischemic cascade. The damage is the result of the build-up of metabolic waste products, inability to maintain cell membranes
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
, mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
l damage, and eventual leakage of autolyzing proteolytic
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called prote ...
enzymes into the cell and surrounding tissues.
Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion injury that can be more damaging than the initial ischemia. Reintroduction of blood flow brings oxygen back to the tissues, causing a greater production of free radicals
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
and reactive oxygen species that damage cells. It also brings more calcium ions to the tissues causing further calcium overloading and can result in potentially fatal cardiac arrhythmia
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
s and also accelerates cellular self-destruction. The restored blood flow also exaggerates the inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
response of damaged tissues, causing white blood cells to destroy damaged cells that may otherwise still be viable.
Treatment
Early treatment is essential to keep the affected organ viable. The treatment options include injection of an anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where t ...
, thrombolysis, embolectomy, surgical revascularization, or partial amputation. Anticoagulant therapy is initiated to prevent further enlargement of the thrombus
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of ...
. Continuous IV unfractionated heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...
has been the traditional agent of choice.[
If the condition of the ischemic limb is stabilized with ]anticoagulation
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
, recently formed emboli
An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule ( fat embolism), a bubble of air or other gas ( gas embolism), amniotic fluid ( amn ...
may be treated with catheter-directed thrombolysis using intra-arterial infusion of a thrombolytic agent (e.g., recombinant tissue plasminogen activator ( tPA), streptokinase, or urokinase
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally ...
). A percutaneous catheter inserted into the femoral artery and threaded to the site of the clot is used to infuse the drug. Unlike anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where t ...
s, thrombolytic agents work directly to resolve the clot over a period of 24 to 48 hours.[
Direct arteriotomy may be necessary to remove the clot. Surgical revascularization may be used in the setting of trauma (e.g., laceration of the artery). Amputation is reserved for cases where limb salvage is not possible. If the patient continues to have a risk of further embolization from some persistent source, such as chronic atrial fibrillation, treatment includes long-term oral ]anticoagulation
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
to prevent further acute arterial ischemic episodes.[
Decrease in body temperature reduces the aerobic metabolic rate of the affected cells, reducing the immediate effects of hypoxia. Reduction of body temperature also reduces the inflammation response and reperfusion injury. For frostbite injuries, limiting thawing and warming of tissues until warmer temperatures can be sustained may reduce reperfusion injury.
Ischemic stroke is at times treated with various levels of statin therapy at hospital discharge, followed by home time, in an attempt to lower the risk of adverse events.
]
Society and culture
The Infarct Combat Project (ICP) is an international nonprofit organization
A nonprofit organization (NPO) or non-profit organisation, also known as a non-business entity, not-for-profit organization, or nonprofit institution, is a legal entity organized and operated for a collective, public or social benefit, in co ...
founded in 1998 to fight ischemic heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...
s through education and research.Infarct Combat Project website
accessed October 26, 2015.
Etymology and pronunciation
The word ''ischemia'' () is from Greek ἴσχαιμος ''iskhaimos'' 'staunching blood', from ἴσχω ''iskhο'' 'keep back, restrain' and αἷμα ''haima'' 'blood'.
See also
* Infarction
Infarction is tissue death ( necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct
(from th ...
* Inhibitor protein
The inhibitor protein (IP) is situated in the mitochondrial matrix and protects the cell against rapid ATP hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used ...
* Trauma triad of death
The trauma triad of death is a medical term describing the combination of hypothermia, acidosis, and coagulopathy. This combination is commonly seen in patients who have sustained severe traumatic injuries and results in a significant rise in ...
*
References
Bibliography
* Elizabeth (editor)
Oxford Reference: ''Concise Medical Dictionary''
(1990, 3rd ed.). Oxford University Press: Market House Books, 1987, 2nd ed., pp. 107,
{{Authority control
Angiology